Biopolymers & Proteomics Core: Project Summary/Abstract The ability to sensitively and quantitatively analyze proteins, peptides, small molecules and metabolites is critical to understanding differences between normal and disease states in cells, tissues and organisms. Such analyses typically require sophisticated technical expertise and state-of-the-art instrumentation. The Biopolymers & Proteomics Core (B&P Core) provides Koch Institute researchers with a diverse range of services, with an emphasis on protein/peptide, proteomic and mass spectrometry services, that enable both synthesis and analysis of biological materials. These are technologies that individual researchers usually do not learn, but are essential for modern cancer research, and as such the Core provides access to these techniques. In the current funding period, the B&P Core added new capabilities and modified existing services, including: acquisition of two new hybrid quadrupole-orbitrap MS instruments with funds from Institutional sources to expand proteomics analysis capacity and improve sensitivity; upgraded HPLC with funds from Institutional sources to enable improved fractionation of complex samples and added independent HPLC use; and expanded expertise in HPLC analysis and purification (e.g. small molecule-drug conjugates). Center Member Core use has been strong: 84% of Center Members use the Core, account for 74% of Core service use, and include investigators from all three Research Programs. In the upcoming period, the B&P Core will continue to offer a wide range of state-of-the-art services to support Center Member research programs, and will evaluate emerging capabilities in the context of Center Member needs and interests. A number of new initiatives are planned, including: expansion and enhancement of proteomics capabilities in global and quantitative proteomic analysis, detection of post-translational modifications and identification of binding partner profiling; and improved investigator support for mass spectrometry-related informatics and complex proteomic data analyses. The B&P Core is also committed to maintaining instrumentation at the leading edge, and will continue to closely monitor technological improvements, particularly with regard to LC-MS instrument sensitivity, specificity, operation, and speed. The Core has taken advantage of leasing and vendor consignment programs to provide more frequent instrumentation updates, allowing the Core to pilot new advances and technologies at lower relative cost. In the upcoming funding period, we will conduct a hands-on assessment of Center Member needs with respect to metabolomics capabilities. Funding for any new equipment acquisitions will be solely from Institutional sources. This Shared Resource is essential to the success of the Koch Institute mission and provides exceptional value to the CCSG. The requested CCSG budget for Year 49 is increased by 18.5% over the Core CCSG budget for the current period (Year 48), reflecting increased support for proteomics expertise.